Variant rs1140412 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_005514.8(HLA-B):c.363C>T(p.Ser121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 3)

Exomes 𝑓: 0.015 ( 95 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Variant links:

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

HLA-B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	3/8	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	3/8		NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes

AF:

0.000995

AC:

AN:

36186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000465

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000735

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000763

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00154

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0318

AC:

5650

AN:

177552

Hom.:

452

AF XY:

0.0321

AC XY:

3098

AN XY:

96486

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.0301

Gnomad SAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.0681

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0151

AC:

11906

AN:

787924

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

5966

AN XY:

393120

show subpopulations

Gnomad4 AFR exome

AF:

0.00480

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.00921

Gnomad4 SAS exome

AF:

0.00982

Gnomad4 FIN exome

AF:

0.0216

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.000995

AC:

AN:

36194

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

16814

show subpopulations

Gnomad4 AFR

AF:

0.000464

Gnomad4 AMR

AF:

0.000734

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000769

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00154

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0383

Hom.:

3333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.1

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over